Muzaffar Khan

A validated CE method for determining dimethylsulfate a carcinogen and chloroacetyl chloride a potential genotoxin at trace levels in drug substances

A simple and rapid capillary zone electrophoretic method was developed for determining dimethyl sulfate a possible human carcinogen and mutagen and chloroacetyl chloride a potential genotoxic agent at trace levels in pharmaceutical drug substances by indirect photometric detection. A systematic screening of various anionic probes was performed to obtain the best separation conditions and sensitivity. High sensitivities with low quantification and detection levels were achieved for dimethylsulfate and chloroacetyl chloride using a background electrolyte (BGE) containing 5 mM pyridine dicarboxylic acid as the probe ion. The method is specific, precise and accurate for the two genotoxins. The optimized method was validated for specificity, precision, linearity, accuracy and stability in solution. Calibration curves were linear (R>0.999) for both dimethylsulfate and chloroacetyl chloride in the range LOQ - 300% of nominal concentrations. The CE method was effectively implemented for estimating dimethylsulfate and chloroacetyl chloride in two different active pharmaceutical ingredients (APIs).

Development and validation of a stability indicating HPLC method for simultaneous determination of four novel fluoroquinolone dimers as potential antibacterial agents.

A series of novel 6-fluoro1,4-dihydro-4-oxo-3-quinoline carboxylic acid dimers were synthesized as potential antibacterial agents from commercially available substituted fluorobenzoic acids. A stability indicating HPLC method was developed to determine these novel fluoroquinolone dimers using a systematic method development approach. Samples were subjected to stress conditions of hydrolysis, oxidation, photolysis and thermal degradation; and analyzed to demonstrate the specificity and stability indicating ability of the developed method. The precision for all four fluoroquinolone dimers was within 2.0% RSD. Calibration curves were linear (LOQ, 150%), with regression coefficients >0.99 for all dimers. The method was conveniently applied for determining purity and assay of these four novel fluoroquinolone dimers.

Complex carbohydrate specificity of lectin from fruiting body of Ganoderma lucidum. A surface plasmon resonance study

The thermodynamics and kinetics of binding of glycans and glycoproteins to Ganoderma lucidum lectin was studied using surface plasmon resonance. The lectin showed highest affinity for asialo triantennary N glycan (Ka = 3.52×105) among the glycans tested. There was a several fold increase in affinity for glycoproteins compared to their corresponding glycans and coincident increase in contribution from enthalpy (ΔH), suggesting the involvement of hydrogen bonding in the interaction as well as involvement of protein‐protein interactions. Increased affinity also showed increase in unfavorable negative binding entropy (ΔS) which was compensated with higher enthalpy. The glycoproteins showed faster association rates (k1) and the activation energy (E†1) in the association process was much lower for the glycoproteins than glycans, resulting in their faster associations. These observations elaborate the role of protein matrix in lectin‐glycoconjugate interaction.